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  • 1.
    Apró, William
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Eva Blomstrand's research group.
    Wang, Li
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Research group for Mitokondriell funktion och metabolisk kontroll.
    Pontén, Marjan
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Blomstrand, Eva
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Eva Blomstrand's research group.
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Research group for Mitokondriell funktion och metabolisk kontroll.
    Endurance Exercise Does Not Impair mTOR Signalling After Resistance Exercise: D-58 Thematic Poster - Skeletal Muscle Cell Signaling: JUNE 2, 2011 3:15 PM - 5:15 PM: ROOM: 3042011In: Medicine & Science in Sports & Exercise, ISSN 0195-9131, E-ISSN 1530-0315, Vol. 43, no 5, p. 52-Article in journal (Other academic)
    Abstract [en]

    Resistance exercise is known to stimulate muscle hypertrophy and this effect is mainly mediated by the mammalian target of rapamycin (mTOR) pathway. In contrast, endurance exercise results in a divergent phenotypic response which to a large extent is mediated by adenosine monophosphate-activated protein kinase (AMPK). Research indicates that molecular interference may exist, possibly through an inhibitory effect on mTOR signalling by AMPK, when these two modes of exercise are combined.

    PURPOSE: To investigate the impact of subsequent endurance exercise on resistance exercise induced mTOR signalling.

    METHODS: In a randomized and cross-over fashion, ten male subjects performed either heavy resistance exercise (R) or heavy resistance exercise followed by endurance exercise (RE) on two separate occasions. The R protocol consisted of thirteen sets of leg press exercise with 3 minutes of recovery allowed between each set. In the RE session, resistance exercise was followed by 15 minutes recovery after which 30 min of cycling was initiated at an intensity equal to 70 % of the subjects' maximal oxygen consumption. Muscle biopsies were collected before, 1 and 3 hours after resistance exercise in both trials. Samples were analyzed for several signalling proteins in the mTOR pathway using western blot technique.

    RESULTS: Phosphorylation of mTOR increased approx. twofold at 1 h post resistance exercise and remained elevated at the 3 h time point (p< 0.01) with no difference between the two trials. Phosphorylation of p70S6k, a downstream target of mTOR, was increased about 6-and18-fold at 1 h and 3 h post resistance exercise (p< 0.01). There was no difference in p70S6k phosphorylation at any time point between the two trials. Phosphorylation of the eukaryotic elongation factor eEF2 was decreased 3- to 4-fold at both time points post resistance exercise (p< 0.01) with no difference between trials. Phosphorylation of AMPK was unchanged at the 1 h time point but decreased approximately 30 % from pre-exercise values in both trials at 3 h post resistance exercise (p< 0.01).

    CONCLUSIONS: The signalling response following heavy resistance exercise is not blunted by subsequent endurance exercise. Supported by the Swedish National Centre for Research in Sports.

  • 2.
    Apró, William
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Eva Blomstrand's research group.
    Wang, Li
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Research group for Mitokondriell funktion och metabolisk kontroll.
    Pontén, Marjan
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Research group for Mitokondriell funktion och metabolisk kontroll.
    Blomstrand, Eva
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Eva Blomstrand's research group.
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Research group for Mitokondriell funktion och metabolisk kontroll.
    Resistance exercise induced mTORC1 signaling is not impaired by subsequent endurance exercise in human skeletal muscle.2013In: American Journal of Physiology. Endocrinology and Metabolism, ISSN 0193-1849, E-ISSN 1522-1555, Vol. 305, no 1, p. E22-32Article in journal (Refereed)
    Abstract [en]

    The current dogma is that the muscle adaptation to resistance exercise is blunted when combined with endurance exercise. The suggested mechanism (based on rodent experiments) is that activation of adenosine monophosphate-activated protein kinase (AMPK) during endurance exercise impairs muscle growth through inhibition of the mechanistic target of rapamycin complex 1 (mTORC1). The purpose of this study was to investigate potential interference of endurance training on the signaling pathway of resistance training [mTORC1 phosphorylation of ribosomal protein S6 kinase 1 (S6K1)] in human muscle. Ten healthy and moderately trained male subjects performed on two separate occasions either acute high-intensity and high-volume resistance exercise (leg press, R) or R followed by 30 min of cycling (RE). Muscle biopsies were collected before and 1 and 3 h post resistance exercise. Phosphorylation of mTOR (Ser(2448)) increased 2-fold (P < 0.05) and that of S6K1 (Thr(389)) 14-fold (P < 0.05), with no difference between R and RE. Phosphorylation of eukaryotic elongation factor 2 (eEF2, Thr(56)) was reduced ∼70% during recovery in both trials (P < 0.05). An interesting finding was that phosphorylation of AMPK (Thr(172)) and acetyl-CoA carboxylase (ACC, Ser(79)) decreased ∼30% and ∼50%, respectively, 3 h postexercise (P < 0.05). Proliferator-activated receptor-γ coactivator-1 (PGC-1α) mRNA increased more after RE (6.5-fold) than after R (4-fold) (RE vs. R: P < 0.01) and was the only gene expressed differently between trials. These data show that the signaling of muscle growth through the mTORC1-S6K1 axis after heavy resistance exercise is not inhibited by subsequent endurance exercise. It is also suggested that prior activation of mTORC1 signaling may repress subsequent phosphorylation of AMPK.

  • 3. Bakkman, Linda
    et al.
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Research group for Mitokondriell funktion och metabolisk kontroll.
    Holmberg, H-C
    Tonkonogi, Michail
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Quantitative and qualitative adaptation of human skeletal muscle mitochondria to hypoxic compared with normoxic training at the same relative work rate.2007In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 190, no 3, p. 243-51Article in journal (Refereed)
    Abstract [en]

    AIM: To investigate if training during hypoxia (H) improves the adaptation of muscle oxidative function compared with normoxic (N) training performed at the same relative intensity. METHOD: Eight untrained volunteers performed one-legged cycle training during 4 weeks in a low-pressure chamber. One leg was trained under N conditions and the other leg under hypobaric hypoxia (526 mmHg) at the same relative intensity as during N (65% of maximal power output, W(max)). Muscle biopsies were taken from vastus lateralis before and after the training period. Muscle samples were analysed for the activities of oxidative enzymes [citrate synthase (CS) and cytochrome c oxidase (COX)] and mitochondrial respiratory function. RESULTS: W(max) increased with more than 30% over the training period during both N and H. CS activity increased significantly after training during N conditions (+20.8%, P < 0.05) but remained unchanged after H training (+4.5%, ns) with a significant difference between conditions (P < 0.05 H vs. N). COX activity was not significantly changed by training and was not different between exercise conditions [+14.6 (N) vs. -2.3% (H), ns]. Maximal ADP stimulated respiration (state 3) expressed per weight of muscle tended to increase after N (+31.2%, P < 0.08) but not after H training (+3.2%, ns). No changes were found in state four respiration, respiratory control index, P/O ratio, mitochondrial Ca(2+) resistance and apparent Km for oxygen. CONCLUSION: The training-induced increase in muscle oxidative function observed during N was abolished during H. Altitude training may thus be disadvantageous for adaptation of muscle oxidative function.

  • 4.
    Berthelson, Per
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Research group for Mitokondriell funktion och metabolisk kontroll.
    Katz, Abram
    Institutionen för Fysiologi och Farmakologi, Karolinska Instititutet.
    Andersson, Eva
    Swedish School of Sport and Health Sciences, GIH.
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Research group for Mitokondriell funktion och metabolisk kontroll.
    Acute exercise and starvation induced insulin resistance2012In: Medicine & Science In Sports & Exercise, 2012, S498 Vol. 44 No. 5 Supplement. 2661., 2012, p. 2661-Conference paper (Other academic)
    Abstract [en]

    It is well known that starvation causes insulin resistance. The mechanism is unclear but may relate disturbances in lipid metabolism i.e. incomplete mitochondrial FA oxidation and/or accumulation of lipid intermediates. Exercise results in increased substrate oxidation and may thus remove interfering lipid metabolites and reverse starvation-induced insulin resistance. However, the effect of acute exercise and starvation on insulin sensitivity is not known.

    Purpose: The aim of this study was to investigate the effect of exercise on starvation-induced insulin resistance and to elucidate potential mechanisms.

    Methods: Nine healthy lean subjects underwent 84h starvation on two occasions separated by at least 2 weeks. The starvation period was followed by either exercise (EX; 5x10 min intervals with 2-4 min rest, starting at 70 %VO2 max) or an equal period of rest (NE). Before and after the starvation period (3h after exercise/rest) subjects were investigated with muscle biopsies, bloo samples and an intravenous glucose tolerance test. Muscle samples were used for measurement of mitochondrial respiration in permeabilized muscle fibers (Oroboros oxygraph), glycogen content and activation of signaling proteins.

    Results: Insulin sensitivity was significantly higher in the EX group compared to the NE group (p<0.05). After starvation mitochondrial respiration was lower in both groups with complex I substrates whereas respiration with complex I+II substrates was higher in EX (p<0.05 vs. basal and NE). Muscle glycogen was decreased to 73% (NE) and 31% (EX) of the basal values. The EX group had a significant increased activation of AS160. Plasma FA increased 3-4 fold to 1.39±0.32(NE) and 1.80±0.49 (EX) (mmol/l) after starvation and plasma beta-hydroxybutyrate increased about 50-fold to 6.43±2.01(NE) and 7.12±1.59 (EX)(mmol/l).

    Conclusion: Acute exercise reverses starvation-induced insulin resistance. Plasma FA and BOH were increased to similar extent after NE and EX and cannot explain the changes in insulin sensitivity. However, an increased substrate oxidation together with the observed increased capacity for mitochondrial FA oxidation after EX may be involved in the activation of AS160 and the reversal of starvation-induced insulin resistance.

  • 5. Bishop, David J
    et al.
    Thomas, Claire
    Moore-Morris, Tom
    Tonkonogi, Michail
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Research group for Mitokondriell funktion och metabolisk kontroll.
    Mercier, Jacques
    Sodium bicarbonate ingestion prior to training improves mitochondrial adaptations in rats.2010In: American Journal of Physiology. Endocrinology and Metabolism, ISSN 0193-1849, E-ISSN 1522-1555, Vol. 299, no 2, p. E225-33Article in journal (Refereed)
    Abstract [en]

    We tested the hypothesis that reducing hydrogen ion accumulation during training would result in greater improvements in muscle oxidative capacity and time to exhaustion (TTE). Male Wistar rats were randomly assigned to one of three groups (CON, PLA, and BIC). CON served as a sedentary control, whereas PLA ingested water and BIC ingested sodium bicarbonate 30 min prior to every training session. Training consisted of seven to twelve 2-min intervals performed five times/wk for 5 wk. Following training, TTE was significantly greater in BIC (81.2 +/- 24.7 min) compared with PLA (53.5 +/- 30.4 min), and TTE for both groups was greater than CON (6.5 +/- 2.5 min). Fiber respiration was determined in the soleus (SOL) and extensor digitorum longus (EDL), with either pyruvate (Pyr) or palmitoyl carnitine (PC) as substrates. Compared with CON (14.3 +/- 2.6 nmol O(2).min(-1).mg dry wt(-1)), there was a significantly greater SOL-Pyr state 3 respiration in both PLA (19.6 +/- 3.0 nmol O(2).min(-1).mg dry wt(-1)) and BIC (24.4 +/- 2.8 nmol O(2).min(-1).mg dry wt(-1)), with a significantly greater value in BIC. However, state 3 respiration was significantly lower in the EDL from both trained groups compared with CON. These differences remained significant in the SOL, but not the EDL, when respiration was corrected for citrate synthase activity (an indicator of mitochondrial mass). These novel findings suggest that reducing muscle hydrogen ion accumulation during running training is associated with greater improvements in both mitochondrial mass and mitochondrial respiration in the soleus.

  • 6.
    Boushel, Robert
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology.
    Lundby, Carsten
    Qvortrup, Klaus
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Mitochondrial plasticity with exercise training and extreme environments.2014In: Exercise and sport sciences reviews, ISSN 0091-6331, E-ISSN 1538-3008, Vol. 42, no 4, p. 169-74Article in journal (Refereed)
    Abstract [en]

    Mitochondria form a reticulum in skeletal muscle. Exercise training stimulates mitochondrial biogenesis, yet an emerging hypothesis is that training also induces qualitative regulatory changes. Substrate oxidation, oxygen affinity, and biochemical coupling efficiency may be regulated differentially with training and exposure to extreme environments. Threshold training doses inducing mitochondrial upregulation remain to be elucidated considering fitness level.

  • 7.
    Fernström, Maria
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Bakkman, Linda
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Tonkonogi, Michail
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Shabalina, Irina
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Rozhdestvenskaya, Z
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Mattsson, C. Mikael
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Björn Ekblom's research group.
    Enqvist, Jonas K
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Björn Ekblom's research group.
    Ekblom, Björn
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Björn Ekblom's research group.
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Reduced efficiency, but increased fat oxidation, in mitochondria from human skeletal muscle after 24-h ultraendurance exercise.2007In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 102, no 5, p. 1844-1849Article in journal (Refereed)
    Abstract [en]

    The hypothesis that ultraendurance exercise influences muscle mitochondrial function has been investigated. Athletes in ultraendurance performance performed running, kayaking, and cycling at 60% of their peak O(2) consumption for 24 h. Muscle biopsies were taken preexercise (Pre-Ex), postexercise (Post-Ex), and after 28 h of recovery (Rec). Respiration was analyzed in isolated mitochondria during state 3 (coupled to ATP synthesis) and state 4 (noncoupled respiration), with fatty acids alone [palmitoyl carnitine (PC)] or together with pyruvate (Pyr). Electron transport chain activity was measured with NADH in permeabilized mitochondria. State 3 respiration with PC increased Post-Ex by 39 and 41% (P < 0.05) when related to mitochondrial protein and to electron transport chain activity, respectively. State 3 respiration with Pyr was not changed (P > 0.05). State 4 respiration with PC increased Post-Ex but was lower than Pre-Ex at Rec (P < 0.05 vs. Pre-Ex). Mitochondrial efficiency [amount of added ADP divided by oxygen consumed during state 3 (P/O ratio)] decreased Post-Ex by 9 and 6% (P < 0.05) with PC and PC + Pyr, respectively. P/O ratio remained reduced at Rec. Muscle uncoupling protein 3, measured with Western blotting, was not changed Post-Ex but tended to decrease at Rec (P = 0.07 vs. Pre-Ex). In conclusion, extreme endurance exercise decreases mitochondrial efficiency. This will increase oxygen demand and may partly explain the observed elevation in whole body oxygen consumption during standardized exercise (+13%). The increased mitochondrial capacity for PC oxidation indicates plasticity in substrate oxidation at the mitochondrial level, which may be of advantage during prolonged exercise.

  • 8.
    Fernström, Maria
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Mogensen, M
    Bagger, M
    Pedersen, PK
    The potential for mitochondrial fat oxidation in human skeletal muscle influences whole body fat oxidation during low-intensity exercise2007In: American journal of physiology. Endocrinology and metabolism, ISSN 0193-1849, Vol. 292, no 1, p. E223-30Article in journal (Refereed)
    Abstract [en]

    The purpose of this study was to investigate fatty acid (FA) oxidation in isolated mitochondrial vesicles (mit) and its relation to training status, fiber type composition, and whole body FA oxidation. Trained (Vo(2 peak) 60.7 +/- 1.6, n = 8) and untrained subjects (39.5 +/- 2.0 ml.min(-1).kg(-1), n = 5) cycled at 40, 80, and 120 W, and whole body relative FA oxidation was assessed from respiratory exchange ratio (RER). Mit were isolated from muscle biopsies, and maximal ADP stimulated respiration was measured with carbohydrate-derived substrate [pyruvate + malate (Pyr)] and FA-derived substrate [palmitoyl-l-carnitine + malate (PC)]. Fiber type composition was determined from analysis of myosin heavy-chain (MHC) composition. The rate of mit oxidation was lower with PC than with Pyr, and the ratio between PC and Pyr oxidation (MFO) varied greatly between subjects (49-93%). MFO was significantly correlated to muscle fiber type distribution, i.e., %MHC I (r = 0.62, P = 0.03), but was not different between trained (62 +/- 5%) and untrained subjects (72 +/- 2%). MFO was correlated to RER during submaximal exercise at 80 (r = -0.62, P = 0.02) and 120 W (r = -0.71, P = 0.007) and interpolated 35% Vo(2 peak) (r = -0.74, P = 0.004). ADP sensitivity of mit respiration was significantly higher with PC than with Pyr. It is concluded that MFO is influenced by fiber type composition but not by training status. The inverse correlation between RER and MFO implies that intrinsic mit characteristics are of importance for whole body FA oxidation during low-intensity exercise. The higher ADP sensitivity with PC than that with Pyr may influence fuel utilization at low rate of respiration.

  • 9.
    Fernström, Maria
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Shabalina, Irina
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Bakkman, Linda
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Tonkonogi, Michail
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Mattsson, C. Mikael
    Swedish School of Sport and Health Sciences, GIH.
    Enqvist, Jonas
    Swedish School of Sport and Health Sciences, GIH.
    Ekblom, Björn
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Björn Ekblom's research group.
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Skeletal muscle mitochondrial function and ROS production in response to extreme endurance exercise in athletes.2006In: 14 European bioenergetic conference, Moscow, Russia, 22-27 July, 2006, 2006Conference paper (Other academic)
    Abstract [en]

    Although it is well known that endurance exercise induces oxidative stress (1) there is no evidence of deteriorated mitochondrial function after 1-2 hours intensive exercise (2). However, the effects of extreme endurance exercise on mitochondrial function and mitochondrial ROS production have not been investigated previously. Nine healthy well-trained men (age 27.1 ± 0.87 (mean ± SE), BMI 24.2 ± 0.64 and VO2 peak 62.5 ± 1.78 ml/kg. min) performed 24 hours exercise, consisting of equal parts running, cycling and paddling. Muscle biopsies were taken from vastus lateralis pre-exercise (PreEx), immediately post-exercise (PostEx) and after 28 hours of recovery (PostEx-28). Mitochondria were isolated and mitochondrial respiration was analyzed with palmitoyl-carnitine (PC) and pyruvate (Pyr). Mitochondrial H2O2 release was measured with the Amplex Red-horseradish peroxide method. The reaction was initiated by addition of succinate with following addition of antimycin A (reversed electron flow). UCP3 protein expression, evaluated with western blot technique, was not changed by exercise. Both state 3 (Pyr and PC) and state 4 (PC) rates of oxygen consumption (estimated per maximal ETC-activity) were increased PostEx (+29%, +11% and +18%). State 3 remained elevated PostEx-28, whereas state 4 (Pyr) decreased below that at PreEx (-18%). Mitochondrial efficiency (P/O) decreased PostEx (Pyr -8.9%, PC -6.1%) and remained reduced PostEx-28. The relative substrate oxidation (state 3 PC/Pyr) increased after exercise PreEx: (0.71 ± 0.06 vs. PostEx (0.90 ±0.04) and (0.77 ±0.06) PostEx-28. Mitochondrial H2O2 release (succinate) increased dramatically after exercise (+189 ± 64%). Treatment with Antimycin A resulted in a twofold-increased rate of mitochondrial H2O2 release PreEx but a decreased rate in PostEx samples. The exercise-induced changes in mitochondrial ROS production was totally abolished PostEx-28. In conclusion extreme endurance exercise decreases mitochondrial efficiency and increases mitochondrial ROS production. Both of these changes would increase the oxygen demand during exercise. Relative fatty acid oxidation as measured in isolated mitochondria increased after exercise indicating that the capacity to oxidize fat is improved during prolonged exercise.

    1. Mastaloudis, A., S.W. Leonard, and M.G. Traber, Oxidative stress in athletes during extreme endurance exercise. Free Radic Biol Med, 2001. 31(7): p. 911-22.

    2. Tonkonogi, M., et al., Mitochondrial function and antioxidative defence in human muscle: effects of endurance training and oxidative stress. J Physiol, 2000. 528 Pt 2: p. 379-88.

  • 10.
    Fernström, Maria
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Tonkonogi, Michail
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Effects of acute and chronic endurance exercise on mitochondrial uncoupling in human skeletal muscle.2004In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 554, p. 755-763Article in journal (Refereed)
    Abstract [en]

    Mitochondrial proteins such as uncoupling protein 3 (UCP3) and adenine nucleotide translocase (ANT) may mediate back-leakage of protons and serve as uncouplers of oxidative phosphorylation. We hypothesized that UCP3 and ANT increase after prolonged exercise and/or endurance training, resulting in increased uncoupled respiration (UCR). Subjects were investigated with muscle biopsies before and after acute exercise (75 min of cycling at 70% of .VO2peak) or 6 weeks endurance training. Mitochondria were isolated and respiration measured in the absence (UCR or state 4) and presence of ADP (coupled respiration or state 3). Protein expression of UCP3 and ANT was measured with Western blotting. After endurance training, .VO2peak, citrate synthase activity (CS), state 3 respiration and ANT increased by 24, 47, 40 and 95%, respectively (all P < 0.05), whereas UCP3 remained unchanged. When expressed per unit of CS (a marker of mitochondrial volume) UCP3 and UCR decreased by 54% and 18%(P < 0.05). CS increased by 43% after acute exercise and remained elevated after 3 h of recovery (P < 0.05), whereas the other muscle parameters remained unchanged. An intriguing finding was that acute exercise reversibly enhanced the capacity of mitochondria to accumulate Ca2+(P < 0.05) before opening of permeability transition pores. In conclusion, UCP3 protein and UCR decrease after endurance training when related to mitochondrial volume. These changes may prevent excessive basal thermogenesis. Acute exercise enhances mitochondrial resistance to Ca2+ overload but does not influence UCR or protein expression of UCP3 and ANT. The increased Ca2+ resistance may prevent mitochondrial degradation and the mechanism needs to be further explored.

  • 11.
    Frank, Per
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Andersson, Eva
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Pontén, Marjan
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology.
    Ekblom, Björn
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Björn Ekblom's and Mats Börjesson's research group.
    Ekblom, Maria
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Laboratory for Biomechanics and Motor Control.
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Strength training improves muscle aerobic capacity and glucose tolerance in elderly2016In: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 26, no 7, p. 764-773Article in journal (Refereed)
    Abstract [en]

    The primary aim of this study was to investigate the effect of short-term resistance training (RET) on mitochondrial protein content and glucose tolerance in elderly. Elderly women and men (age 71 ± 1, mean ± SEM) were assigned to a group performing 8 weeks of resistance training (RET, n = 12) or no training (CON, n = 9). The RET group increased in (i) knee extensor strength (concentric +11 ± 3%, eccentric +8 ± 3% and static +12 ± 3%), (ii) initial (0-30 ms) rate of force development (+52 ± 26%) and (iii) contents of proteins related to signaling of muscle protein synthesis (Akt +69 ± 20 and mammalian target of rapamycin +69 ± 32%). Muscle fiber type composition changed to a more oxidative profile in RET with increased amount of type IIa fibers (+26.9 ± 6.8%) and a trend for decreased amount of type IIx fibers (-16.4 ± 18.2%, P = 0.068). Mitochondrial proteins (OXPHOS complex II, IV, and citrate synthase) increased in RET by +30 ± 11%, +99 ± 31% and +29 ± 8%, respectively. RET resulted in improved oral glucose tolerance measured as reduced area under curve for glucose (-21 ± 26%) and reduced plasma glucose 2 h post-glucose intake (-14 ± 5%). In CON parameters were unchanged or impaired. In conclusion, short-term resistance training in elderly not only improves muscular strength, but results in robust increases in several parameters related to muscle aerobic capacity.

  • 12.
    Frank, Per
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Research group for Mitokondriell funktion och metabolisk kontroll.
    Katz, Abram
    Institutionen för Fysiologi och Farmakologi, Karolinska Institutet.
    Andersson, Eva
    Swedish School of Sport and Health Sciences, GIH.
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Research group for Mitokondriell funktion och metabolisk kontroll.
    Acute exercise during starvation improves insulin sensitivity and increases mitochondrial FA oxidation2012Conference paper (Other academic)
    Abstract [en]

    Aim: To investigate if exercise can reverse starvation-induced insulin resistance and to elucidate the mechanism. Methods: Nine subjects underwent 87 h of starvation with (EX) or without (NE) one exercise session at the end. Before and after starvation (3 h post-exercise) subjects underwent an intravenous glucose tolerance test and muscle biopsy. Results: Insulin sensitivity decreased after starvation (NE) but increased after exercise (EX). Glycogen stores were reduced and plasma FA and β-Hydroxybutyrate increased in both conditions. Mitochondrial respiration with FA substrate increased in EX but was unchanged in NE. RCR and mitochondrial ROS production decreased in both conditions. Phosphorylation of Acetyl-CoA carboxylase (ACC) and Akt substrate of 160 kDA (AS160) proteins increased in EX. Conclusion: Exercise improves starvation induced insulin resistance, probably by increased mitochondrial FA oxidation, reduced glycogen stores and alterations in signaling proteins involved in glucose uptake and FA metabolism.

  • 13.
    Frank, Per
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Research group for Mitokondriell funktion och metabolisk kontroll.
    Katz, Abram
    Karolinska Institutet.
    Andersson, Eva
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Research group for Mitokondriell funktion och metabolisk kontroll.
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Research group for Mitokondriell funktion och metabolisk kontroll.
    Acute exercise reverses starvation-mediated insulin resistance in humans.2013In: American Journal of Physiology. Endocrinology and Metabolism, ISSN 0193-1849, E-ISSN 1522-1555, Vol. 304, no 4, p. E436-43Article in journal (Refereed)
    Abstract [en]

    Within 2-3 days of starvation, pronounced insulin resistance develops, possibly mediated by increased lipid load. Here, we show that one exercise bout increases mitochondrial fatty acid (FA) oxidation and reverses starvation-induced insulin resistance. Nine healthy subjects underwent 75-h starvation on two occasions: with no exercise (NE) or with one exercise session at the end of the starvation period (EX). Muscle biopsies were analyzed for mitochondrial function, contents of glycogen, and phosphorylation of regulatory proteins. Glucose tolerance and insulin sensitivity, measured with an intravenous glucose tolerance test (IVGTT), were impaired after starvation, but in EX the response was attenuated or abolished. Glycogen stores were reduced, and plasma FA was increased in both conditions, with a more pronounced effect in EX. After starvation, mitochondrial respiration decreased with complex I substrate (NE and EX), but in EX there was an increased respiration with complex I + II substrate. EX altered regulatory proteins associated with increases in glucose disposal (decreased phosphorylation of glycogen synthase), glucose transport (increased phosphorylation of Akt substrate of 160 kDa), and FA oxidation (increased phosphorylation of acetyl-CoA carboxylase). In conclusion, exercise reversed starvation-induced insulin resistance and was accompanied by reduced glycogen stores, increased lipid oxidation capacity, and activation of signaling proteins involved in glucose transport and FA metabolism.

  • 14. Gejl, Kasper
    et al.
    Hvid, Lars G
    Frandsen, Ulrik
    Jensen, Kurt
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Ortenblad, Niels
    Muscle Glycogen Content Modifies SR Ca2 + Release Rate in Elite Endurance Athletes.2014In: Medicine & Science in Sports & Exercise, ISSN 0195-9131, E-ISSN 1530-0315, Vol. 46, no 3, p. 496-505Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The aim of the present study was to investigate the influence of muscle glycogen content on sarcoplasmic reticulum (SR) function and peak power output (Wpeak) in elite endurance athletes.

    METHODS: Fourteen highly trained male triathletes (VO2max 66.5 ± 1.3 ml O2 kg min), performed 4h of glycogen depleting cycling exercise (HRmean 73 ± 1% of maximum). During the first 4h recovery, athletes received either water (H2O) or carbohydrate (CHO), separating alterations in muscle glycogen content from acute changes affecting SR function and performance. Thereafter, all subjects received CHO enriched food for the remaining 20h recovery.

    RESULTS: Immediately following exercise, muscle glycogen content and SR Ca release rate was reduced to 32 ± 4% (225 ± 28 mmol kg dw) and 86 ± 2% of initial levels, respectively (P < 0.01). Glycogen markedly recovered after 4h recovery with CHO (61 ± 2% of pre) and SR Ca release rate returned to pre-exercise level. However, in the absence of CHO during the first 4h recovery, glycogen and SR Ca release rate remained depressed, with normalization of both parameters at the end of the 24h recovery after receiving a CHO enriched diet. Linear regression demonstrated a significant correlation between SR Ca release rate and muscle glycogen content (P < 0.01, r = 0.30). The 4h cycling exercise reduced Wpeak by 5.5-8.9% at different cadences (P < 0.05) and Wpeak was normalized after 4h recovery with CHO whereas Wpeak remained depressed (P < 0.05) following water provision. Wpeak was fully recovered after 24h in both the H2O and the CHO group.

    CONCLUSION: In conclusion, the present results suggest that low muscle glycogen depresses muscle SR Ca release rate, which may contribute to fatigue and delayed recovery of Wpeak 4 hours post exercise.

  • 15. Hey-Mogensen, M
    et al.
    Højlund, K
    Vind, B F
    Wang, Li
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Dela, F
    Beck-Nielsen, H
    Fernström, Maria
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Effect of physical training on mitochondrial respiration and reactive oxygen species release in skeletal muscle in patients with obesity and type 2 diabetes.2010In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 53, no 9, p. 1976-85Article in journal (Refereed)
    Abstract [en]

    AIM/HYPOTHESIS: Studies have suggested a link between insulin resistance and mitochondrial dysfunction in skeletal muscles. Our primary aim was to investigate the effect of aerobic training on mitochondrial respiration and mitochondrial reactive oxygen species (ROS) release in skeletal muscle of obese participants with and without type 2 diabetes. METHODS: Type 2 diabetic men (n = 13) and control (n = 14) participants matched for age, BMI and physical activity completed 10 weeks of aerobic training. Pre- and post-training muscle biopsies were obtained before a euglycaemic-hyperinsulinaemic clamp and used for measurement of respiratory function and ROS release in isolated mitochondria. RESULTS: Training significantly increased insulin sensitivity, maximal oxygen consumption and muscle mitochondrial respiration with no difference between groups. When expressed in relation to a marker of mitochondrial density (intrinsic mitochondrial respiration), training resulted in increased mitochondrial ADP-stimulated respiration (with NADH-generating substrates) and decreased respiration without ADP. Intrinsic mitochondrial respiration was not different between groups despite lower insulin sensitivity in type 2 diabetic participants. Mitochondrial ROS release tended to be higher in participants with type 2 diabetes. CONCLUSIONS/INTERPRETATION: Aerobic training improves muscle respiration and intrinsic mitochondrial respiration in untrained obese participants with and without type 2 diabetes. These adaptations demonstrate an increased metabolic fitness, but do not seem to be directly related to training-induced changes in insulin sensitivity.

  • 16. Iaia, F Marcello
    et al.
    Hellsten, Ylva
    Nielsen, Jens Jung
    Fernström, Maria
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Bangsbo, Jens
    Four weeks of speed endurance training reduces energy expenditure during exercise and maintains muscle oxidative capacity despite a reduction in training volume.2009In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 106, no 1, p. 73-80Article in journal (Refereed)
    Abstract [en]

    We studied the effect of an alteration from regular endurance to speed endurance training on muscle oxidative capacity, capillarization, as well as energy expenditure during submaximal exercise and its relationship to mitochondrial uncoupling protein 3 (UCP3) in humans. Seventeen endurance-trained runners were assigned to either a speed endurance training (SET; n = 9) or a control (Con; n = 8) group. For a 4-wk intervention (IT) period, SET replaced the ordinary training ( approximately 45 km/wk) with frequent high-intensity sessions each consisting of 8-12 30-s sprint runs separated by 3 min of rest (5.7 +/- 0.1 km/wk) with additional 9.9 +/- 0.3 km/wk at low running speed, whereas Con continued the endurance training. After the IT period, oxygen uptake was 6.6, 7.6, 5.7, and 6.4% lower (P < 0.05) at running speeds of 11, 13, 14.5, and 16 km/h, respectively, in SET, whereas remained the same in Con. No changes in blood lactate during submaximal running were observed. After the IT period, the protein expression of skeletal muscle UCP3 tended to be higher in SET (34 +/- 6 vs. 47 +/- 7 arbitrary units; P = 0.06). Activity of muscle citrate synthase and 3-hydroxyacyl-CoA dehydrogenase, as well as maximal oxygen uptake and 10-km performance time, remained unaltered in both groups. In SET, the capillary-to-fiber ratio was the same before and after the IT period. The present study showed that speed endurance training reduces energy expenditure during submaximal exercise, which is not mediated by lowered mitochondrial UCP3 expression. Furthermore, speed endurance training can maintain muscle oxidative capacity, capillarization, and endurance performance in already trained individuals despite significant reduction in the amount of training.

  • 17. Jensen, Line
    et al.
    Gejl, Kasper D
    Ørtenblad, Niels
    Nielsen, Jakob L
    Bech, Rune D
    Nygaard, Tobias
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Frandsen, Ulrik
    Carbohydrate restricted recovery from long term endurance exercise does not affect gene responses involved in mitochondrial biogenesis in highly trained athletes.2015In: Physiological Reports, E-ISSN 2051-817X, Vol. 3, no 2Article in journal (Refereed)
    Abstract [en]

    The aim was to determine if the metabolic adaptations, particularly PGC-1α and downstream metabolic genes were affected by restricting CHO following an endurance exercise bout in trained endurance athletes. A second aim was to compare baseline expression level of these genes to untrained. Elite endurance athletes (VO2max 66 ± 2 mL·kg(-1)·min(-1), n = 15) completed 4 h cycling at ~56% VO2max. During the first 4 h recovery subjects were provided with either CHO or only H2O and thereafter both groups received CHO. Muscle biopsies were collected before, after, and 4 and 24 h after exercise. Also, resting biopsies were collected from untrained subjects (n = 8). Exercise decreased glycogen by 67.7 ± 4.0% (from 699 ± 26.1 to 239 ± 29.5 mmol·kg(-1)·dw(-1)) with no difference between groups. Whereas 4 h of recovery with CHO partly replenished glycogen, the H2O group remained at post exercise level; nevertheless, the gene expression was not different between groups. Glycogen and most gene expression levels returned to baseline by 24 h in both CHO and H2O. Baseline mRNA expression of NRF-1, COX-IV, GLUT4 and PPAR-α gene targets were higher in trained compared to untrained. Additionally, the proportion of type I muscle fibers positively correlated with baseline mRNA for PGC-1α, TFAM, NRF-1, COX-IV, PPAR-α, and GLUT4 for both trained and untrained. CHO restriction during recovery from glycogen depleting exercise does not improve the mRNA response of markers of mitochondrial biogenesis. Further, baseline gene expression of key metabolic pathways is higher in trained than untrained.

  • 18. Jeppesen, Jacob
    et al.
    Mogensen, Martin
    Prats, Clara
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Research group for Mitokondriell funktion och metabolisk kontroll.
    Madsen, Klavs
    Kiens, Bente
    Copenhagen University.
    FAT/CD36 is localized in sarcolemma and in vesicle-like structures in subsarcolemma regions but not in mitochondria.2010In: Journal of Lipid Research, ISSN 0022-2275, E-ISSN 1539-7262, Vol. 51, no 6, p. 1504-12Article in journal (Refereed)
    Abstract [en]

    The primary aim of the present study was to investigate in which cellular compartments fatty acid trans-locase CD36 (FAT/CD36) is localized. Intact and fully functional skeletal muscle mitochondria were isolated from lean and obese female Zucker rats and from 10 healthy male individuals. FAT/CD36 could not be detected in the isolated mitochondria, whereas the mitochondrial marker F(1)ATPase-beta was clearly detected using immunoblotting. Lack of markers for other membrane structures indicated that the mitochondria were not contaminated with membranes known to contain FAT/CD36. In addition, fluorescence immunocytochemistry was performed on single muscle fibers dissected from soleus muscle of lean and obese Zucker rats and from the vastus lateralis muscle from humans. Costaining against FAT/CD36 and MitoNEET clearly show that FAT/CD36 is highly present in sarcolemma and it also associates with some vesicle-like intracellular compartments. However, FAT/CD36 protein was not detected in mitochondrial membranes, supporting the biochemical findings. Based on the presented data, FAT/CD36 seems to be abundantly expressed in sarcolemma and in vesicle-like structures throughout the muscle cell. However, FAT/CD36 is not present in mitochondria in rat or human skeletal muscle. Thus, the functional role of FAT/CD36 in lipid transport seems primarily to be allocated to the plasma membrane in skeletal muscle.

  • 19.
    Larsen, Filip
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Björn Ekblom's research group.
    Ekblom, Björn
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Björn Ekblom's research group.
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Research group for Mitokondriell funktion och metabolisk kontroll.
    Mitochondrial oxygen affinity predicts basal metabolic rate in humans2011In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 25, no 8, p. 2843-52Article in journal (Refereed)
    Abstract [en]

    The basal metabolic rate (BMR) is referred to as the minimal rate of metabolism required to support basic body functions. It is well known that individual BMR varies greatly, even when correcting for body weight, fat content, and thyroid hormone levels, but the mechanistic determinants of this phenomenon remain unknown. Here, we show in humans that mass-related BMR correlates strongly to the mitochondrial oxygen affinity (p50(mito); R(2)=0.66, P=0.0004) measured in isolated skeletal muscle mitochondria. A similar relationship was found for oxygen affinity and efficiency during constant-load submaximal exercise (R(2)=0.46, P=0.007). In contrast, BMR did not correlate to overall mitochondrial density or to proton leak. Mechanistically, part of the p50(mito) seems to be controlled by the excess of cytochrome c oxidase (COX) protein and activity relative to other mitochondrial proteins. This is illustrated by the 5-fold increase in p50(mito) after partial cyanide inhibition of COX at doses that do not affect maximal mitochondrial electron flux through the ETS. These data suggest that the interindividual variation in BMR in humans is primarily explained by differences in mitochondrial oxygen affinity. The implications of these findings are discussed in terms of a trade-off between aerobic efficiency and power.

  • 20.
    Larsen, Filip
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Björn Ekblom's research group.
    Ekblom, Björn
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Björn Ekblom's research group.
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Weitzberg, Eddie
    Lundberg, Jon
    Effects of dietary nitrate on blood pressure in healthy volunteers2006In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 28, no 355(26), p. 2792-3Article in journal (Refereed)
    Abstract [en]

    To the Editor:

    Nitric oxide, generated by nitric oxide synthase, is a key regulator of vascular integrity. This system is dysfunctional in many cardiovascular disorders, including hypertension. A fundamentally different pathway for the generation of nitric oxide was recently described in which the anions nitrate (NO3 ) and nitrite (NO2 ) are converted into nitric oxide and other bioactive nitrogen oxides.1-3 Nitrate is abundant in our diet, and particularly high levels are found in many vegetables.3

    We examined the effect of 3-day dietary supplementation with either sodium nitrate (at a dose of 0.1 mmol per kilogram of body weight per day) or placebo (sodium chloride, at a dose of 0.1 mmol per kilogram per day) on blood pressure in 17 physically active, healthy volunteers, none of whom smoked (15 men and 2 women; mean age, 24 years). The study had a randomized, double-blind, crossover design with two different treatment periods during which the subjects received either nitrate or placebo; the treatment periods were separated by a washout period of at least 10 days. The compounds were dissolved in water and could not be distinguished by taste or appearance. During the two treatment periods, the subjects were instructed to avoid all foods with a moderate or high nitrate content.3

    Systolic blood pressure Effects of 3-Day Dietary Supplementation with Inorganic Nitrate or Placebo on Systolic (Panel A) and Diastolic (Panel B) Blood Pressure in 17 Healthy Volunteers.) and pulse rate did not change significantly after nitrate supplementation, as compared with placebo supplementation. However, the diastolic blood pressure was on average 3.7 mm Hg lower after nitrate supplementation than after placebo supplementation (P<0.02) (Figure 1B), and the mean arterial pressure was 3.2 mm Hg lower (P<0.03). Plasma nitrate levels were higher after nitrate ingestion than after placebo ingestion (mean [±SD], 178±51 and 26±11 μM, respectively; P<0.001), as were plasma nitrite levels (219±105 and 138±38 nM, respectively; P<0.01).

    The daily nitrate dose used in the study corresponds to the amount normally found in 150 to 250 g of a nitrate-rich vegetable such as spinach, beetroot, or lettuce. It is clear from earlier studies, such as the Dietary Approaches to Stop Hypertension (DASH) trial, that a diet rich in fruits and vegetables can reduce blood pressure,4,5 but attempts to modify single nutrients have been inconsistent. Therefore, it has been argued that the effect of any individual nutrient is too small to detect in trials. In our study, reduced blood pressure was associated with nitrate supplementation alone; this effect was evident in young normotensive subjects. In fact, it was similar to that seen in the healthy control group in the DASH study.4 The exact mechanism behind the blood-pressure–lowering effect of nitrate needs to be clarified in future studies.

    We conclude that short-term dietary supplementation with inorganic nitrate reduces diastolic blood pressure in healthy young volunteers.

  • 21.
    Larsen, Filip
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Björn Ekblom's research group.
    Schiffer, TA
    Borniquel, S
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Research group for Mitokondriell funktion och metabolisk kontroll.
    Ekblom, Björn
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Björn Ekblom's research group.
    Lundberg, JO
    Weitzberg, E
    Dietary inorganic nitrate improves mitochondrial efficiency in humans.2011In: Cell Metabolism, ISSN 1550-4131, Vol. 13, no 2, p. 149-159Article in journal (Refereed)
    Abstract [en]

    Nitrate, an inorganic anion abundant in vegetables, is converted in vivo to bioactive nitrogen oxides including NO. We recently demonstrated that dietary nitrate reduces oxygen cost during physical exercise, but the mechanism remains unknown. In a double-blind crossover trial we studied the effects of a dietary intervention with inorganic nitrate on basal mitochondrial function and whole-body oxygen consumption in healthy volunteers. Skeletal muscle mitochondria harvested after nitrate supplementation displayed an improvement in oxidative phosphorylation efficiency (P/O ratio) and a decrease in state 4 respiration with and without atractyloside and respiration without adenylates. The improved mitochondrial P/O ratio correlated to the reduction in oxygen cost during exercise. Mechanistically, nitrate reduced the expression of ATP/ADP translocase, a protein involved in proton conductance. We conclude that dietary nitrate has profound effects on basal mitochondrial function. These findings may have implications for exercise physiology- and lifestyle-related disorders that involve dysfunctional mitochondria.

  • 22. Mogensen, M
    et al.
    Vind, B F
    Højlund, K
    Beck-Nielsen, H
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Research group for Mitokondriell funktion och metabolisk kontroll.
    Maximal lipid oxidation in patients with type 2 diabetes is normal and shows an adequate increase in response to aerobic training.2009In: Diabetes, obesity and metabolism, ISSN 1462-8902, E-ISSN 1463-1326, Vol. 11, no 9, p. 874-83Article in journal (Refereed)
    Abstract [en]

    AIM: Insulin resistance in subjects with type 2 diabetes (T2D) and obesity is associated with an imbalance between the availability and the oxidation of lipids. We hypothesized that maximal whole-body lipid oxidation during exercise (FATmax) is reduced and that training-induced metabolic adaptation is attenuated in T2D. METHODS: Obese T2D (n = 12) and control (n = 11) subjects matched for age, sex, physical activity and body mass index completed 10 weeks of aerobic training. Subjects were investigated before and after training with maximal and submaximal exercise tests and euglycaemic-hyperinsulinaemic clamps combined with muscle biopsies. RESULTS: Training increased maximal oxygen consumption (VO(2max)) and muscle citrate synthase activity and decreased blood lactate concentrations during submaximal exercise in both groups (all p < 0.01). FATmax increased markedly (40-50%) in both T2D and control subjects after training (all p < 0.001). There were no significant differences in these variables and lactate threshold (%VO(2max)) between groups before or after training. Insulin-stimulated glucose disappearance rate (Rd) was lower in T2D vs. control subjects both before and after training. Rd increased in response to training in both groups (all p < 0.01). There was no correlation between Rd and measures of oxidative capacity or lipid oxidation during exercise or the training-induced changes in these parameters. CONCLUSIONS: FATmax was not reduced in T2D, and muscle oxidative capacity increased adequately in response to aerobic training in obese subjects with and without T2D. These metabolic adaptations to training seem to be unrelated to changes in insulin sensitivity and indicate that an impaired capacity for lipid oxidation is not a major cause of insulin resistance in T2D.

  • 23. Mogensen, Martin
    et al.
    Bagger, Malene
    Pedersen, Preben
    Fernstrom, Maria
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Cycling efficiency in humans is related to low UCP3 content and to type I fibres but not to mitochondrial efficiency2006In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 571, no 3, p. 669-681Article in journal (Refereed)
    Abstract [en]

    The purpose of this study was to investigate the hypothesis that cycling efficiency in vivo is related to mitochondrial efficiency measured in vitro and to investigate the effect of training status on these parameters. Nine endurance trained and nine untrained male subjects ( , respectively) completed an incremental submaximal efficiency test for determination of cycling efficiency (gross efficiency, work efficiency (WE) and delta efficiency). Muscle biopsies were taken from m. vastus lateralis and analysed for mitochondrial respiration, mitochondrial efficiency (MEff; i.e. P/O ratio), UCP3 protein content and fibre type composition (% MHC I). MEff was determined in isolated mitochondria during maximal (state 3) and submaximal (constant rate of ADP infusion) rates of respiration with pyruvate. The rates of mitochondrial respiration and oxidative phosphorylation per muscle mass were about 40% higher in trained subjects but were not different when expressed per unit citrate synthase (CS) activity (a marker of mitochondrial density). Training status had no influence on WE (trained 28.0 +/- 0.5, untrained 27.7 +/- 0.8%, N.S.). Muscle UCP3 was 52% higher in untrained subjects, when expressed per muscle mass (P < 0.05 versus trained). WE was inversely correlated to UCP3 (r=-0.57, P < 0.05) and positively correlated to percentage MHC I (r= 0.58, P < 0.05). MEff was lower (P < 0.05) at submaximal respiration rates (2.39 +/- 0.01 at 50% ) than at state 3 (2.48 +/- 0.01) but was neither influenced by training status nor correlated to cycling efficiency. In conclusion cycling efficiency was not influenced by training status and not correlated to MEff, but was related to type I fibres and inversely related to UCP3. The inverse correlation between WE and UCP3 indicates that extrinsic factors may influence UCP3 activity and thus MEff in vivo.

  • 24. Mogensen, Martin
    et al.
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Research group for Mitokondriell funktion och metabolisk kontroll.
    Mitochondrial efficiency in rat skeletal muscle: influence of respiration rate, substrate and muscle type.2006In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 185, p. 229-236Article in journal (Refereed)
    Abstract [en]

    Aim: To investigate the hypothesis that mitochondrial efficiency (i.e. P/O ratio) is higher in type I than in type II fibres during submaximal rates of respiration.

    Methods: Mitochondria were isolated from rat soleus and extensor digitorum longus (EDL) muscles, representing type I and type II fibres, respectively. Mitochondrial efficiency (P/O ratio) was determined with pyruvate (Pyr) or palmitoyl-L-carnitine (PC) during submaximal (constant rate of ADP infusion) and maximal (Vmax, state 3) rates of respiration and fitted to monoexponential functions.

    Results: There was no difference in Vmax between PC and Pyr in soleus but in EDL Vmax with PC was only 58% of that with Pyr. The activity of 3-hydroxyacyl-CoA dehydrogenase (HAD) was 3-fold higher in soleus than in EDL. P/O ratio at Vmax was 8-9% lower with PC (2.33±0.02 (soleus) and 2.30±0.02 (EDL)) than with Pyr (2.52±0.03 (soleus) and 2.54±0.03 (EDL)) but not different between the two muscles (P>0.05). P/O ratio was low at low rates of respiration and increased exponentially when the rate of respiration increased. The asymptotes of the curves were similar to P/O ratio at Vmax. P/O ratio at submaximal respirations was not different between soleus and EDL neither with Pyr nor with PC.

    Conclusion: Mitochondrial efficiency, as determined in vitro, was not significantly different in the two fibre types neither at Vmax nor at submaximal rates of respiration. The low Vmax for PC oxidation in EDL may relate to low activity of β-oxidation.

  • 25. Nielsen, Joachim
    et al.
    Mogensen, Martin
    Vind, Birgitte F
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Research group for Mitokondriell funktion och metabolisk kontroll.
    Højlund, Kurt
    Schrøder, Henrik D
    Ortenblad, Niels
    Increased subsarcolemmal lipids in type 2 diabetes: effect of training on localization of lipids, mitochondria, and glycogen in sedentary human skeletal muscle.2010In: American Journal of Physiology. Endocrinology and Metabolism, ISSN 0193-1849, E-ISSN 1522-1555, Vol. 298, no 3, p. E706-13Article in journal (Refereed)
    Abstract [en]

    The purpose of the study was to investigate the effect of aerobic training and type 2 diabetes on intramyocellular localization of lipids, mitochondria, and glycogen. Obese type 2 diabetic patients (n = 12) and matched obese controls (n = 12) participated in aerobic cycling training for 10 wk. Endurance-trained athletes (n = 15) were included for comparison. Insulin action was determined by euglycemic-hyperinsulinemic clamp. Intramyocellular contents of lipids, mitochondria, and glycogen at different subcellular compartments were assessed by transmission electron microscopy in biopsies obtained from vastus lateralis muscle. Type 2 diabetic patients were more insulin resistant than obese controls and had threefold higher volume of subsarcolemmal (SS) lipids compared with obese controls and endurance-trained subjects. No difference was found in intermyofibrillar lipids. Importantly, following aerobic training, this excess SS lipid volume was lowered by approximately 50%, approaching the levels observed in the nondiabetic subjects. A strong inverse association between insulin sensitivity and SS lipid volume was found (r(2)=0.62, P = 0.002). The volume density and localization of mitochondria and glycogen were the same in type 2 diabetic patients and control subjects, and showed in parallel with improved insulin sensitivity a similar increase in response to training, however, with a more pronounced increase in SS mitochondria and SS glycogen than in other localizations. In conclusion, this study, estimating intramyocellular localization of lipids, mitochondria, and glycogen, indicates that type 2 diabetic patients may be exposed to increased levels of SS lipids. Thus consideration of cell compartmentation may advance the understanding of the role of lipids in muscle function and type 2 diabetes.

  • 26. Ortenblad, Niels
    et al.
    Macdonald, Will A
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Research group for Mitokondriell funktion och metabolisk kontroll.
    Glycolysis in contracting rat skeletal muscle is controlled by factors related to energy state.2009In: Biochemical Journal, ISSN 0264-6021, E-ISSN 1470-8728, Vol. 420, no 2, p. 161-8Article in journal (Refereed)
    Abstract [en]

    The control of glycolysis in contracting muscle is not fully understood. The aim of the present study was to examine whether activation of glycolysis is mediated by factors related to the energy state or by a direct effect of Ca2+ on the regulating enzymes. Extensor digitorum longus muscles from rat were isolated, treated with cyanide to inhibit aerobic ATP production and stimulated (0.2 s trains every 4 s) until force was reduced to 70% of initial force (control muscle, referred to as Con). Muscles treated with BTS (N-benzyl-p-toluene sulfonamide), an inhibitor of cross-bridge cycling without affecting Ca2+ transients, were stimulated for an equal time period as Con. Energy utilization by the contractile apparatus (estimated from the observed relation between ATP utilization and force-time integral) was 60% of total. In BTS, the force-time integral and ATP utilization were only 38 and 58% of those in Con respectively. Glycolytic rate in BTS was only 51% of that in Con but the relative contribution of ATP derived from PCr (phosphocreatine) and glycolysis and the relation between muscle contents of PCr and Lac (lactate) were not different. Prolonged cyanide incubation of quiescent muscle (low Ca2+) did not change the relation between PCr and Lac. The reduced glycolytic rate in BTS despite maintained Ca2+ transients, and the unchanged PCr/Lac relation in the absence of Ca2+ transients, demonstrates that Ca2+ is not the main trigger of glycogenolysis. Instead the preserved relative contribution of energy delivered from PCr and glycolysis during both conditions suggests that the glycolytic rate is controlled by factors related to energy state.

  • 27.
    Psilander, Niklas
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Frank, Per
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Flockhart, Mikael
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Adding strength to endurance training does not enhance aerobic capacity in cyclists2015In: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 25, no 4, p. e353-e359Article in journal (Refereed)
    Abstract [en]

    The molecular signaling of mitochondrial biogenesis is enhanced when resistance exercise is added to a bout of endurance exercise. The purpose of the present study was to examine if this mode of concurrent training translates into increased mitochondrial content and improved endurance performance. Moderately trained cyclists performed 8 weeks (two sessions per week) of endurance training only (E, n = 10; 60-min cycling) or endurance training followed by strength training (ES, n = 9; 60-min cycling + leg press). Muscle biopsies were obtained before and after the training period and analyzed for enzyme activities and protein content. Only the ES group increased in leg strength (+19%, P < 0.01), sprint peak power (+5%, P < 0.05), and short-term endurance (+9%, P < 0.01). In contrast, only the E group increased in muscle citrate synthase activity (+11%, P = 0.06), lactate threshold intensity (+3%, P < 0.05), and long-term endurance performance (+4%, P < 0.05). Content of mitochondrial proteins and cycling economy was not affected by training. Contrary to our hypothesis, the results demonstrate that concurrent training does not enhance muscle aerobic capacity and endurance performance in cyclists.

  • 28.
    Psilander, Niklas
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Frank, Per
    Flockhart, Mikael
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Exercise with low glycogen increases PGC-1α gene expression in human skeletal muscle.2013In: European Journal of Applied Physiology, ISSN 1439-6319, E-ISSN 1439-6327, Vol. 113, no 4, p. 951-963Article in journal (Refereed)
    Abstract [en]

    Recent studies suggest that carbohydrate restriction can improve the training-induced adaptation of muscle oxidative capacity. However, the importance of low muscle glycogen on the molecular signaling of mitochondrial biogenesis remains unclear. Here, we compare the effects of exercise with low (LG) and normal (NG) glycogen on different molecular factors involved in the regulation of mitochondrial biogenesis. Ten highly trained cyclists (VO(2max) 65 ± 1 ml/kg/min, W (max) 387 ± 8 W) exercised for 60 min at approximately 64 % VO(2max) with either low [166 ± 21 mmol/kg dry weight (dw)] or normal (478 ± 33 mmol/kg dw) muscle glycogen levels achieved by prior exercise/diet intervention. Muscle biopsies were taken before, and 3 h after, exercise. The mRNA of peroxisome proliferator-activated receptor-γ coactivator-1 was enhanced to a greater extent when exercise was performed with low compared with normal glycogen levels (8.1-fold vs. 2.5-fold increase). Cytochrome c oxidase subunit I and pyruvate dehydrogenase kinase isozyme 4 mRNA were increased after LG (1.3- and 114-fold increase, respectively), but not after NG. Phosphorylation of AMP-activated protein kinase, p38 mitogen-activated protein kinases and acetyl-CoA carboxylase was not changed 3 h post-exercise. Mitochondrial reactive oxygen species production and glutathione oxidative status tended to be reduced 3 h post-exercise. We conclude that exercise with low glycogen levels amplifies the expression of the major genetic marker for mitochondrial biogenesis in highly trained cyclists. The results suggest that low glycogen exercise may be beneficial for improving muscle oxidative capacity.

  • 29.
    Psilander, Niklas
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Research group for Mitokondriell funktion och metabolisk kontroll.
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Research group for Mitokondriell funktion och metabolisk kontroll.
    Nya forskningsrön kan ge bättre träningsmetoder2013In: Svensk Idrottsforskning: Organ för Centrum för Idrottsforskning, ISSN 1103-4629, Vol. 22, no 1, p. 41-44Article in journal (Other academic)
    Abstract [sv]

    Det finns många uppfattningar om hur man bäst förbättrar konditionen. Ofta förlitar idrottare sig mer på beprövad erfarenhet än på vetenskapen. Men under de senaste åren har idrottsforskningen, med hjälp av molekylärbiologisk teknik, gjort framsteg i hur man kan effektivisera sin träning genom kosten och sättet att träna.

  • 30.
    Psilander, Niklas
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Research group for Mitokondriell funktion och metabolisk kontroll.
    Wang, Li
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Research group for Mitokondriell funktion och metabolisk kontroll.
    Westergren, Jens
    Tonkonogi, Michail
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Research group for Mitokondriell funktion och metabolisk kontroll.
    Mitochondrial gene expression in elite cyclists: effects of high-intensity interval exercise.2010In: European Journal of Applied Physiology, ISSN 1439-6319, E-ISSN 1439-6327, Vol. 110, no 3, p. 597-606Article in journal (Refereed)
    Abstract [en]

    Little is known about the effect of training on genetic markers for mitochondrial biogenesis in elite athletes. We tested the hypothesis that low-volume sprint interval exercise (SIE) would be as effective as high-volume interval exercise (IE). Ten male cyclists competing on national elite level (W (max) 403 ± 13 W, VO(2peak) 68 ± 1 mL kg(-1) min(-1)) performed two interval exercise protocols: 7 × 30-s "all-out" bouts (SIE) and 3 × 20-min bouts at ~87% of VO(2peak) (IE). During IE, the work was eightfold larger (1,095 ± 43 vs. 135 ± 5 kJ) and the exercise duration 17 times longer (60 vs. 3.5 min) than during SIE. Muscle samples were taken before and 3 h after exercise. The mRNA of upstream markers of mitochondrial biogenesis [peroxisome proliferator-activated receptor-γ coactivator-1 (PGC-1α), PGC-1α-related coactivator (PRC) and peroxisome proliferator-activated receptor δ (PPARδ)] increased to the same extent after SIE and IE (6-, 1.5- and 1.5-fold increase, respectively). Of the downstream targets of PGC-1α, mitochondrial transcription factor A (Tfam) increased only after SIE and was significantly different from that after IE (P < 0.05), whereas others increased to the same extent (pyruvate dehydrogenase kinase, PDK4) or was unchanged (nuclear respiratory factor 2, NRF2). We conclude that upstream genetic markers of mitochondrial biogenesis increase in a similar way in elite athletes after one exercise session of SIE and IE. However, since the volume and duration of work was considerably lower during SIE and since Tfam, the downstream target of PGC-1α, increased only after SIE, we conclude that SIE might be a time-efficient training strategy for highly trained individuals.

  • 31.
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Research group for Mitokondriell funktion och metabolisk kontroll.
    Boosting fat burning with carnitine: an old friend comes out from the shadow.2011In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 589, no Pt 7, p. 1509-10Article in journal (Refereed)
  • 32.
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Research group for Mitokondriell funktion och metabolisk kontroll.
    Comments on Point: Counterpoint: Muscle lactate and H⁺ production do/do not have a 1:1 association in skeletal muscle. Why add complexity/confusion to a simple issue?2011In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 110, no 5, p. 1494-Article in journal (Refereed)
  • 33.
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Research group for Mitokondriell funktion och metabolisk kontroll.
    Control of lipid oxidation at the mitochondrial level.2009In: Applied physiology, nutrition, and metabolism = Physiologie appliquée, nutrition et métabolisme, ISSN 1715-5312, Vol. 34, no 3, p. 382-8Article in journal (Refereed)
    Abstract [en]

    The rate of lipid oxidation during exercise is controlled at several sites, and there is a reciprocal dependency between oxidation of lipids and carbohydrates (CHO). It is well known that the proportion of the 2 fuels oxidized is influenced by substrate availability and exercise intensity, but the mechanisms regulating fuel preferences remain unclear. During intense exercise, oxidation of long-chain fatty acids (LCFAs) decreases, and the major control is likely to be at the mitochondrial level. Potential mitochondrial sites for control of lipid oxidation include transport of LCFAs into mitochondrial matrix, beta-oxidation, the tricarboxylic acid cycle, and the electron transport chain (ETC). CHO catabolism may impair lipid oxidation by interfering with the transfer of LCFAs into mitochondria and by competing for mutual cofactors (i.e., nicotinamide adenine dinucleotide and (or) coenzyme A (CoA)). The different effect of energy state on the catabolism of CHO and lipids is likely to be of major importance in explaining the shift in fuel utilization during intensive exercise. Formation of acetyl-CoA from CHO is activated by a low energy state, and will lead to accumulation of products that are inhibitory to lipid oxidation. In contrast, beta-oxidation of LCFAs to acetyl-CoA is not stimulated by a low energy state. Further interaction between CHO and LCFAs may occur by substrate competition for electron carriers at ETC, due to provisions of electrons through different complexes. Feedback inhibition of beta-oxidation by redox state is thought to be an important mechanism for the slowing of lipid oxidation during intensive exercise.

  • 34.
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Fysiologisk forskning åren 1992-20132014In: Från Kungl. Gymnastiska Centralinstitutet till Gymnastik- och idrottshögskolan: en betraktelse av de senaste 25 åren som del av en 200-årig historia / [ed] Suzanne Lundvall, Stockholm: Gymnastik- och idrottshögskolan, GIH , 2014, p. 194-199Chapter in book (Other (popular science, discussion, etc.))
  • 35.
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Mitochondrial function during exercise2016In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 216, no S707, p. S06-1-Article in journal (Refereed)
  • 36.
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Research group for Mitokondriell funktion och metabolisk kontroll.
    Mitokondrier och arbetsfysiologi2013In: Idrottsmedicin, ISSN 2001-3302, no 2, p. 23-25Article in journal (Other academic)
    Abstract [sv]

    Forskning på mitokondriefunktion tillför viktig kunskap om mekanismen till förändringar i träningssvar. Forskning på hur träning med låga glykogennivåer påverkar gener för mitokondrietillväxt är ett exempel på detta.

  • 37.
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Muscle energetics during explosive activities and potential effects of nutrition and training.2014In: Sports Medicine, ISSN 0112-1642, E-ISSN 1179-2035, Vol. 44, no Suppl 2, p. 167-73Article in journal (Refereed)
    Abstract [en]

    The high-energy demand during high-intensity exercise (HIE) necessitates that anaerobic processes cover an extensive part of the adenosine triphosphate (ATP) requirement. Anaerobic energy release results in depletion of phosphocreatine (PCr) and accumulation of lactic acid, which set an upper limit of anaerobic ATP production and thus HIE performance. This report focuses on the effects of training and ergogenic supplements on muscle energetics and HIE performance. Anaerobic capacity (i.e. the amount of ATP that can be produced) is determined by the muscle content of PCr, the buffer capacity and the volume of the contracting muscle mass. HIE training can increase buffer capacity and the contracting muscle mass but has no effect on the concentration of PCr. Dietary supplementation with creatine (Cr), bicarbonate, or beta-alanine has a documented ergogenic effect. Dietary supplementation with Cr increases muscle Cr and PCr and enhances performance, especially during repeated short periods of HIE. The ergogenic effect of Cr is related to an increase in temporal and spatial buffering of ATP and to increased muscle buffer capacity. Bicarbonate loading increases extracellular buffering and can improve performance during HIE by facilitating lactic acid removal from the contracting muscle. Supplementation with beta-alanine increases the content of muscle carnosine, which is an endogenous intracellular buffer. It is clear that performance during HIE can be improved by interventions that increase the capacity of anaerobic ATP production, suggesting that energetic constraints set a limit for performance during HIE.

  • 38.
    Sahlin, Kent
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Research group for Mitokondriell funktion och metabolisk kontroll.
    Harris, R C
    Control of lipid oxidation during exercise: role of energy state and mitochondrial factors.2008In: Acta physiologica (Oxford, England), ISSN 1748-1716, Vol. 194, no 4, p. 283-91Article in journal (Refereed)
    Abstract [en]

    Despite considerable progress during recent years our understanding of how lipid oxidation (LOx) is controlled during exercise remains incomplete. This review focuses on the role of mitochondria and energy state in the control of LOx. LOx increases in parallel with increased energy demand up to an exercise intensity of about 50-60% of VO(2max) after which the contribution of lipid decreases. The switch from lipid to carbohydrate (CHO) is of energetic advantage due to the increased ATP/O(2) yield. In the low-intensity domain (<50%VO(2max)) a moderate reduction in energy state will stimulate both LOx and CHO oxidation and relative fuel utilization is mainly controlled by substrate availability and the capacity of the metabolic pathways. In the high-intensity domain (>60%VO(2max)) there is a pronounced decrease in energy state, which will stimulate glycolysis in excess of the substrate requirements of the oxidative processes. This will lead to acidosis, reduced levels of free Coenzyme A (CoASH) and reduced levels of free carnitine. Acidosis and reduced carnitine may limit the carnitine-mediated transfer of long-chain fatty acids (LCFA) into mitochondria and may thus explain the observed reduction in LOx during high-intensity exercise. Another potential mechanism, suggested in this review, is that Acyl-CoA synthetase (ACS), an initial step in LCFA catabolism, functions as a regulator of LOx. ACS activity is suggested to be under control of CoASH and energy state. Furthermore, evidence exists that additional control points exist beyond mitochondrial FA influx. The nature and site of this control remain to be investigated.

  • 39.
    Sahlin, Kent
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Research group for Mitokondriell funktion och metabolisk kontroll.
    Harris, Roger C
    The creatine kinase reaction: a simple reaction with functional complexity.2011In: Amino Acids, ISSN 0939-4451, E-ISSN 1438-2199, Vol. 40, no 5, p. 1363-7Article in journal (Refereed)
    Abstract [en]

    The classical role of PCr is seen as a reservoir of high-energy phosphates defending cellular ATP levels under anaerobic conditions, high rates of energy transfer or rapid fluctuations in energy requirement. Although the high concentration of PCr in glycolytic fast-twitch fibers supports the role of PCr as a buffer of ATP, the primary importance of the creatine kinase (CK) reaction may in fact be to counteract large increases in ADP, which could otherwise inhibit cellular ATPase-mediated systems. A primary role for CK in the maintenance of ADP homeostasis may explain why, in many conditions, there is an inverse relationship between PCr and muscle contractility but not between ATP and muscle contractility. The high rate of ATP hydrolysis during muscle contraction combined with restricted diffusion of ADP suggests that ADP concentration increases transiently during the contraction phase (ADP spikes) and that these are synchronized with the contraction. The presence of CK, structurally bound in close vicinity to the sites of ATP utilization, will reduce the amplitude and duration of the ADP spikes through PCr-mediated phosphotransfer. When PCr is reduced, the efficiency of CK as an ATP buffer will be reduced and the changes in ADP will become more prominent. The presence of ADP spikes is supported by the finding that other processes known to be activated by ADP (i.e. AMP deamination and glycolysis) are stimulated during exercise but not during anoxia, despite the same low global energy state. Breakdown of PCr is driven by increases in ADP above that depicted by the CK equilibrium and the current method to calculate ADPfree from the CK reaction in a contracting muscle is therefore questionable.

  • 40.
    Sahlin, Kent
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Nielsen, Jens Steen
    Mogensen, Martin
    Tonkonogi, Michail
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Repeated static contractions increase mitochondrial vulnerability towards oxidative stress in human skeletal muscle2007In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 101, p. 833-839Article in journal (Refereed)
    Abstract [en]

    Repeated static contractions (RSC) induce large fluctuations in tissue oxygen tension and increase the generation of reactive oxygen species (ROS). This study investigated the effect of RSC on muscle contractility, mitochondrial respiratory function, and in vitro sarcoplasmatic reticulum (SR) Ca2+-kinetics in human muscle. Ten male subjects performed 5 bouts of static knee extension with 10 min rest in between. Each bout of RSC (target torque 66% of maximal voluntary contraction torque, MVC) was maintained to fatigue. Muscle biopsies were taken pre-exercise and 0.3 and 24 h post-exercise from vastus lateralis. Mitochondria were isolated and respiratory function measured after incubation with H2O2 (HPX) or control medium (CON). Mitochondrial function was not affected by RSC during CON. However, RSC exacerbated mitochondrial dysfunction during HPX resulting in decreased respiratory control index, decreased mitochondrial efficiency (P/O ratio) and increased non-coupled respiration (HPX/CON post vs. pre-exercise). SR Ca2+ uptake rate was lower 0.3 h vs. 24 h post-exercise, whereas SR Ca2+ release rate was unchanged. RSC resulted in long-lasting changes in muscle contractility including reduced maximal torque, low frequency fatigue (LFF) and faster torque relaxation. It is concluded that RSC increases mitochondrial vulnerability towards ROS, reduces SR Ca2+ uptake rate and causes LFF. Although conclusive evidence is lacking we suggest that these changes are related to increased formation of ROS during RSC.

  • 41.
    Sahlin, Kent
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Research group for Mitokondriell funktion och metabolisk kontroll.
    Sallstedt, E-K
    Bishop, D
    Tonkonogi, Michail
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Turning down lipid oxidation during heavy exercise--what is the mechanism?2008In: Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, ISSN 1899-1505, Vol. 59 Suppl 7, p. 19-30Article in journal (Refereed)
    Abstract [en]

    A high potential for lipid oxidation is a sign of metabolic fitness and is important not only for exercise performance but also for health promotion. Despite considerable progress during recent years, our understanding of how lipid oxidation is controlled remains unclear. The rate of lipid oxidation reaches a peak at 50-60% of V(O2 max) after which the contribution of lipids decreases both in relative and absolute terms. In the high-intensity domain (>60% V(O2 max)), there is a pronounced decrease in energy state, which will stimulate the glycolytic rate in excess of the substrate requirements of mitochondrial oxidative processes. Accumulation of glycolytic products will impair lipid oxidation through an interaction with the carnitine-mediated transfer of FA into mitochondria. Another potential site of control is Acyl-CoA synthetase (ACS), which is the initial step in FA catabolism. The activity of ACS may be under control of CoASH and energy state. There is evidence that additional control points exist beyond mitochondrial influx of fatty acids. The electron transport chain (ETC) with associated feed-back control by redox state is one suggested candidate. In this review it is suggested that the control of FA oxidation during heavy exercise is distributed between ACS, CPT1, and ETC.

  • 42.
    Sahlin, Kent
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Research group for Mitokondriell funktion och metabolisk kontroll.
    Seger, Jan
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Effects of prolonged exercise on the contractile properties of human quadriceps muscle.1995In: European Journal of Applied Physiology and Occupational Physiology, ISSN 0301-5548, E-ISSN 1432-1025, Vol. 71, p. 180-186Article in journal (Refereed)
    Abstract [en]

    The contractile properties of the quadriceps muscle were measured in seven healthy male subjects before, during and after prolonged cycling to exhaustion. Special efforts were made to obtain measurements immediately after exercise. The exercise intensity corresponded to about 75% of estimated maximal O2 uptake and time to exhaustion was mean 85 (SEM 9) min. At the end of the cycling heart rate and perceived exertion for the legs were 94% and 97% of maximal values, respectively. Maximal voluntary isometric force (MVC) had decreased after 5 min of exercise to a mean 91 (SEM 4)% of the pre-exercise value (P < 0.05) and decreased further to a mean 82 (SEM 6) and mean 66 (SEM 5)% after 40-min cycling and at exhaustion, respectively. A new finding was that during recovery reversal of MVC occurred in different phases where the half recovery time of the initial rapid phase was about 2 min. The MVC was a mean 80 (SEM 2)% of the pre-exercise value after 30 min and was not affected by superimposed electrical stimulation. Maximal voluntary concentric and eccentric forces decreased to 74% and 80% of initial values at exhaustion (P < 0.05). The kinetics of isometric contraction expressed as the time between 5% and 50% of tension (rise time) and the time between 95% and 50% of tension (relaxation time) were not significantly affected by the prolonged cycling. The electromechanical delay measured as the time between the first electrical stimulus and 5% of tension decreased from a mean 32 (SEM 1) ms at rest to a mean 26.6 (SEM 0.6) ms at fatigue (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

  • 43.
    Sahlin, Kent
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Shabalina, Irina G
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology. Stockholm University.
    Mattsson, C Mikael
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Björn Ekblom's research group.
    Bakkman, Linda
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology. Karolinska Institutet.
    Fernström, Maria
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology. Karolinska Institutet.
    Rozhdestvenskaya, Zinaida
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology.
    Enqvist, Jonas K
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Björn Ekblom's research group.
    Nedergaard, Jan
    Stockholm University.
    Ekblom, Björn T
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Björn Ekblom's research group.
    Tonkonogi, Michail
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology. University of Dalarna.
    Ultra-endurance exercise increases the production of reactive oxygen species in isolated mitochondria from human skeletal muscle.2010In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 108, no 4, p. 780-787Article in journal (Refereed)
    Abstract [en]

    Exercise-induced oxidative stress is important for the muscular adaptation to training but may also cause muscle damage. We hypothesized that prolonged exercise would increase mitochondrial production of reactive oxygen species (ROS) measured in vitro and that this correlates with oxidative damage. Eight male athletes (24-32 years) performed ultra-endurance exercise (kayaking/running/cycling) with an average work intensity of 55% VO2peak for 24 h. Muscle biopsies were taken from vastus lateralis before exercise, immediately after exercise and after 28 h of recovery. The production of H2O2 was measured fluorometrically in isolated mitochondria with the Amplex red and peroxidase system. Succinate-supported mitochondrial H2O2 production was significantly increased after exercise (73% higher, P=0.025) but restored to the initial level at recovery. Plasma level of free fatty acids (FFA) increased 4-fold and exceeded 1.2 mmol l(-1) during the last 6 h of exercise. Plasma FFA at the end of exercise was significantly correlated to mitochondrial ROS production (r=0.74, P<0.05). Mitochondrial content of 4-hydroxy-nonenal-adducts (a marker of oxidative damage) was increased only after recovery and was not correlated with mitochondrial ROS production. Total thiol-group level and glutathione peroxidase activity were elevated after recovery. In conclusion: ultra-endurance exercise increases ROS production in isolated mitochondria but this is reversed after 28 h recovery. Mitochondrial ROS production was not correlated with oxidative damage of mitochondrial proteins, which was increased at recovery but not immediately after exercise. Key words: antioxidative defence, fatty acids, oxidative stress.

  • 44.
    Sahlin, Kent
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Tonkonogi, Michail
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Fernström, Maria
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    The leaky mitochondrion.2004In: Physiology News, Vol. 56, p. 27-28Article in journal (Other academic)
  • 45. Svensson, M
    et al.
    Malm, C
    Tonkonogi, Michail
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Ekblom, Björn
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Björn Ekblom's research group.
    Sjödin, B
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Research group for Mitokondriell funktion och metabolisk kontroll.
    Effect of Q10 supplementation on tissue Q10 levels and adenine nucleotide catabolism during high-intensity exercise.1999In: International Journal of Sport Nutrition, ISSN 1050-1606, Vol. 9, no 2, p. 166-80Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to investigate the concentration of ubiquinone-10 (Q10), at rest, in human skeletal muscle and blood plasma before and after a period of high-intensity training with or without Q10 supplementation. Another aim was to explore whether adenine nucleotide catabolism, lipid peroxidation, and mitochondrial function were affected by Q10 treatment. Seventeen young healthy men were assigned to either a control (placebo) or Q10-supplementation (120 mg/day) group. Q10 supplementation resulted in a significantly higher plasma Q10/total cholesterol level on Days 11 and 20 compared with Day 1. There was no significant change in the concentration of Q10 in skeletal muscle or in isolated skeletal muscle mitochondria in either group. Plasma hypoxanthine and uric acid concentrations increased markedly after each exercise test session in both groups. After the training period, the postexercise increase in plasma hypoxanthine was markedly reduced in both groups, but the response was partially reversed after the recovery period. It was concluded that Q10 supplementation increases the concentration of Q10 in plasma but not in skeletal muscle.

  • 46.
    Tonkonogi, Michail
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Fernström, Maria
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Walsh, Brandon
    Ji, Li Li
    Rooyackers, Olav
    Hammarqvist, Folke
    Wernerman, Jan
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Reduced oxidative power but unchanged antioxidative capacity in skeletal muscle from aged humans.2003In: Pflügers Archiv: European Journal of Physiology, ISSN 0031-6768, E-ISSN 1432-2013, Vol. 446, no 2, p. 261-9Article in journal (Refereed)
    Abstract [en]

    The hypothesis that the aging process is associated with mitochondrial dysfunction and oxidative stress has been investigated in human skeletal muscle. Muscle biopsy samples were taken from seven old male subjects [OS; 75 (range 61-86) years] and eight young male subjects [YS; 25 (22-31) years]. Oxidative function was measured both in permeabilised muscle fibres and isolated mitochondria. Despite matching the degree of physical activity, OS had a lower training status than YS as judged from pulmonary maximal O(2) consumption ( Vdot;O(2)max, -36%) and handgrip strength (-20%). Both maximal respiration and creatine-stimulated respiration were reduced in muscle fibres from OS (-32 and -34%, respectively). In contrast, respiration in isolated mitochondria was similar in OS and YS. The discrepancy might be explained by a biased harvest of "healthy" mitochondria and/or disruption of structural components during the process of isolation. Cytochrome C oxidase was reduced (-40%, P<0.01), whereas UCP3 protein tended to be elevated in OS ( P=0.09). Generation of reactive oxygen species by isolated mitochondria and measures of antioxidative defence (muscle content of glutathione, glutathione redox status, antioxidative enzymes activity) were not significantly different between OS and YS. It is concluded that aging is associated with mitochondrial dysfunction, which appears to be unrelated to reduced physical activity. The hypothesis of increased oxidative stress in aged muscle could not be confirmed in this study.

  • 47.
    Tonkonogi, Michail
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Harris, B
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Research group for Mitokondriell funktion och metabolisk kontroll.
    Mitochondrial oxidative function in human saponin-skinned muscle fibres: effects of prolonged exercise.1998In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 510 ( Pt 1), p. 279-86Article in journal (Refereed)
    Abstract [en]

    1. The influence of prolonged exhaustive exercise on mitochondrial oxidative function was investigated in ten men. 2. Muscle biopsies were taken before and after exercise and mitochondrial respiration investigated in fibre bundles made permeable by pretreatment with saponin. 3. After exercise, respiration in the absence of ADP increased by 18 % (P < 0.01), but respiration at suboptimal ADP concentration (0.1 mM) and maximal ADP-stimulated respiration (1 mM ADP) remained unchanged. 4. In the presence of creatine (20 mM), mitochondrial affinity for ADP increased markedly and respiration at suboptimal ADP concentration (0.1 mM) was similar (pre-exercise) or higher (post-exercise; P < 0.05) than with 1 mM ADP alone. The increase in respiratory rate with creatine was correlated to the relative type I fibre area (r = 0.84). Creatine-stimulated respiration increased after prolonged exercise (P < 0.01). 5. The respiratory control index (6.8 +/- 0.4, mean +/- s.e.m.) and the ratio between respiration at 0.1 and 1 mM ADP (ADP sensitivity index, 0.63 +/- 0.03) were not changed after exercise. The sensitivity index was negatively correlated to the relative type I fibre area (r = -0.86). 6. The influence of exercise on muscle oxidative function has for the first time been investigated with the skinned-fibre technique. It is concluded that maximal mitochondrial oxidative power is intact or improved after prolonged exercise, while uncoupled respiration is increased. The latter finding may contribute to the elevated post-exercise oxygen consumption. The finding that the sensitivity of mitochondrial respiration for ADP and creatine are related to fibre-type composition indicates intrinsic differences in the control of mitochondrial respiration between fibres.

  • 48.
    Tonkonogi, Michail
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Research group for Mitokondriell funktion och metabolisk kontroll.
    Physical exercise and mitochondrial function in human skeletal muscle.2002In: Exercise and sport sciences reviews, ISSN 0091-6331, E-ISSN 1538-3008, Vol. 30, no 3, p. 129-37Article in journal (Refereed)
    Abstract [en]

    Muscle adaptation to endurance training involves qualitative changes in intrinsic properties of mitochondria. After training, the ADP sensitivity of miitochondrion is decreased whereas the effect of creatine on respiration is increased. This results in an improved control of aerobic energy production. Acute exercise does not adversely affect mitochondrial function.

  • 49.
    Tonkonogi, Michail
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Walsh, Brandon
    Tiivel, T
    Saks, V
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Research group for Mitokondriell funktion och metabolisk kontroll.
    Mitochondrial function in human skeletal muscle is not impaired by high intensity exercise.1999In: Pflügers Archiv: European Journal of Physiology, ISSN 0031-6768, E-ISSN 1432-2013, Vol. 437, no 4, p. 562-8Article in journal (Refereed)
    Abstract [en]

    The hypothesis that high-intensity (HI) intermittent exercise impairs mitochondrial function was investigated with different microtechniques in human muscle samples. Ten male students performed three bouts of cycling at 130% of peak O2 consumption (V.O2,peak). Muscle biopsies were taken from the vastus lateralis muscle at rest, at fatigue and after 110 min recovery. Mitochondrial function was measured both in isolated mitochondria and in muscle fibre bundles made permeable with saponin (skinned fibres). In isolated mitochondria there was no change in maximal respiration, rate of adenosine 5'-triphosphate (ATP) production (measured with bioluminescence) and respiratory control index after exercise or after recovery. The ATP production per consumed oxygen (P/O ratio) also remained unchanged at fatigue but decreased by 4% (P<0.05) after recovery. In skinned fibres, maximal adenosine 5'-diphosphate (ADP)-stimulated respiration increased by 23% from rest to exhaustion (P<0.05) and remained elevated after recovery, whereas the respiratory rates in the absence of ADP and at 0.1 mM ADP (submaximal respiration) were unchanged. The ratio between respiration at 0.1 and 1 mM ADP (ADP sensitivity index) decreased at fatigue (P<0.05) but after the recovery period was not significantly different from that at rest. It is concluded that mitochondrial oxidative potential is maintained or improved during exhaustive HI exercise. The finding that the sensitivity of mitochondrial respiration to ADP is reversibly decreased after strenuous exercise may indicate that the control of mitochondrial respiration is altered.

  • 50. Walsh, B
    et al.
    Tonkonogi, Michail
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Söderlund, Karin
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Hultman, E
    Saks, V
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Research group for Mitokondriell funktion och metabolisk kontroll.
    The role of phosphorylcreatine and creatine in the regulation of mitochondrial respiration in human skeletal muscle.2001In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 537, no Pt 3, p. 971-8Article in journal (Refereed)
    Abstract [en]

    1. The role of phosphorylcreatine (PCr) and creatine (Cr) in the regulation of mitochondrial respiration was investigated in permeabilised fibre bundles prepared from human vastus lateralis muscle. 2. Fibre respiration was measured in the absence of ADP (V(0)) and after sequential additions of submaximal ADP (0.1 mM ADP, V(submax)), PCr (or Cr) and saturating [ADP] (V(max)). 3. V(submax) increased by 55 % after addition of saturating creatine (P < 0.01; n = 8) and half the maximal effect was obtained at 5 mM [Cr]. In contrast, V(submax) decreased by 54 % after addition of saturating phosphorylcreatine (P < 0.01; n = 8) and half the maximal effect was obtained at 1 mM [PCr]. V(max) was not affected by Cr or PCr. 4. V(submax) was similar when PCr and Cr were added simultaneously at concentrations similar to those in muscle at rest (PCr/Cr = 2) and at low-intensity exercise (PCr/Cr = 0.5). At conditions mimicking high-intensity exercise (PCr/Cr = 0.1), V(submax) increased to 60 % of V(max) (P < 0.01 vs. rest and low-intensity exercise). 5. Eight of the subjects participated in a 16 day Cr supplementation programme. Following Cr supplementation, V(0) decreased by 17 % (P < 0.01 vs. prior to Cr supplementation), whereas ADP-stimulated respiration (with and without Cr or PCr) was unchanged. 6. For the first time evidence is given that PCr is an important regulator of mitochondrial ADP-stimulated respiration. Phosphorylcreatine decreases the sensitivity of mitochondrial respiration to ADP whereas Cr has the opposite effect. During transition from rest to high-intensity exercise, decreases in the PCr/Cr ratio will effectively increase the sensitivity of mitochondrial respiration to ADP. The decrease in V(0) after Cr supplementation indicates that intrinsic changes in membrane proton conductance occur.

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